| Project/Area Number |
18K08394
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54020:Connective tissue disease and allergy-related
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| Research Institution | Hokkaido University of Science |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
伊藤 萌子 北海道科学大学, 薬学部, 講師 (60711827)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | Werner症候群 / アデノシンデアミナーゼ / アイソザイム / ADA1 / ADA2 / 炎症 / 糖鎖 / 早老症 / 自己炎症性疾患 / ADA / 糖鎖修飾 |
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| Outline of Final Research Achievements |
The pathophysiology of Werner syndrome (WS), the representative hereditary progeroid syndrome, has been suggested to be based on chronic inflammation. On the other hand, adenosine deaminase (ADA), which is a purine nucleotide metabolizing enzyme, has two isozymes, ADA1 and ADA2, and it is known that ADA2 is particularly involved in inflammatory diseases.
When serum ADA isozymes activities were measured, ADA2 activity increased with aging in healthy subjects, and WS patients showed the same tendency as elderly patients. This showed the same behavior as high-sensitivity CRP, which is an inflammatory marker. In addition, sugar chain analysis of ADA2 revealed that sugar chains are important for dimer formation and activity expression during the intracellular synthesis process.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では共に炎症に関与するWSとADA2関連疾患の病態解明に寄与することを目的として、健常人とWS患者の血中ADA活性について比較検討するとともに、ADA2のタンパク質としての機能解析を行った。今回我々が用いた幅広い年齢層（0から100歳）での健常人のADA活性に関する報告はこれまでなされておらず、老化とともにADA2活性が上昇していたことは、inflammaging（炎症性老化）という観点からも新しい知見である。また、ADA2の細胞内での酵素活性発現等に糖鎖が関与することが明らかになったことは、今後のADA2関連疾患の解明にもつながる基礎的データとして意義がある。
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